Healthcare resource utilization and costs among children with cystic fibrosis in the United States.

BACKGROUND: Adverse health impacts of cystic fibrosis (CF) can be present in children before respiratory complications are observed. Children with CF show progressive health decline, with increasing lung function decline in adolescence. This study aims to quantify the healthcare resource utilization (HCRU) and costs attributable to CF by comparing children with CF with the general pediatric population. METHODS: This retrospective, cross-sectional, observational study compared HCRU and costs among children with CF in the US with demographically similar children without CF (comparison group) over a 12-month period using administrative claims data spanning 2010-2017. Analyses were conducted by insurance type (commercially insured [COM] and Medicaid insured [MED]) and stratified by age (<2 years, 2 to <6 years, 6 to <12 years, and 12-17 years). RESULTS: Children with CF (2831 COM and 1896 MED) were matched to children in the comparison group (8493 COM and 5688 MED). Higher prevalence of comorbidities was seen in children with CF versus the comparison group across all ages. Across all ages, HCRU attributable to CF was substantial (higher hospitalization rates, more outpatient and emergency room visits, and greater use of prescription medications), and there were higher associated costs (all p values < .05), in COM and MED populations. HCRU and costs attributable to CF were highest for children aged 12-17 years. CONCLUSIONS: Substantial HCRU and costs are evident among children with CF across all ages, starting as young as infancy, with highest HCRU and costs among adolescents. Effective treatments from an early age are needed for children with CF.

The burden of cystic fibrosis in the Medicaid population.

PURPOSE: To conduct an analysis describing clinical characteristics, pulmonary exacerbation (PEx) events, and health care resource utilization among Medicaid-insured patients with cystic fibrosis (CF). PATIENTS AND METHODS: A retrospective analysis of the Truven Health MarketScan® Medicaid Multi-State administrative claims database (2010-2014) was undertaken. Patients aged ≥6 years with a CF diagnosis, continuously enrolled for 12 months, were identified. Demographics, comorbidities, PEx events, and health care resource utilization and costs over a 12-month enrollment period were analyzed for all patients and by age groups. RESULTS: In total, 1196 patients with CF aged ≥6 years were identified from a sample size of approximately 10 million Medicaid patients. Mean (SD) age was 16.1 (8.8) years. A greater proportion of patients were in younger age groups (6-11 years: 35.5%, 12-17 years: 29.1%, 18-26 years: 25.6%, 27-34 years: 6.7%, ≥35 years: 3.2%). Across all age groups, approximately 90% of patients had at least 1 PEx event; 50.7% of those had a PEx event involving treatment with intravenous antibiotics, and 42.8% required hospitalization. PEx recurrence was frequent: 55.7% of all patients experienced ≥3 PEx events during 1 year. Mean (SD) health care expenditures during a PEx event rose with increasing age, ranging from US$44,589 (US$139,024) to US$116,169 (US$387,752). Overall health care resource utilization was high among patients with CF; 47.2% of the population required an inpatient admission, and 26.8% had subsequent hospitalizations totaling 29.1 days per year in hospital. CONCLUSION: High rates of PEx, hospitalizations, and time spent in hospital demonstrate the significant health care burden of CF among Medicaid beneficiaries.

Economic analysis and budget impact of clostridial collagenase ointment compared with medicinal honey for treatment of pressure ulcers in the US.

OBJECTIVES: Pressure ulcer (PU) treatment poses significant clinical and economic challenges to health-care systems. The aim of this study was to assess the cost-effectiveness and budget impact of enzymatic debridement with clostridial collagenase ointment (CCO) compared with autolytic debridement with medicinal honey (MH) for PU treatment from a US payer/Medicare perspective in the hospital outpatient department setting. METHODS: A cost-effectiveness analysis using a Markov model was developed using a 1-week cycle length across a 1-year time horizon. The three health states were inflammation/senescence, granulation/proliferation (ie, patients achieving 100% granulation), and epithelialization. Data sources included the US Wound Registry, Medicare fee schedules, and other published clinical and cost studies about PU treatment. RESULTS: In the base case analysis over a 1-year time horizon, CCO was the economically dominant strategy (ie, simultaneously conferring greater benefit at less cost). Patients treated with CCO experienced 22.7 quality-adjusted life weeks (QALWs) at a cost of $6,161 over 1 year, whereas MH patients experienced 21.9 QALWs at a cost of $7,149. Patients treated with CCO achieved 11.5 granulation weeks and 6.0 epithelization weeks compared with 10.6 and 4.4 weeks for MH, respectively. The number of clinic visits was 40.1 for CCO vs 43.4 for MH, and the number of debridements was 12.3 for CCO compared with 17.6 for MH. Probabilistic sensitivity analyses determined CCO dominant in 72% of 10,000 iterations and cost-effective in 91%, assuming a benchmark willingness-to-pay threshold of $50,000/quality-adjusted life year ($962/QALW). The budget impact analysis showed that for every 1% of patients shifted from MH to CCO, a cost savings of $9,883 over 1 year for a cohort of 1,000 patients was observed by the payer. CONCLUSION: The results of these economic analyses suggest that CCO is a cost-effective, economically dominant alternative to MH in the treatment of patients with PUs in the hospital outpatient department setting.

Retrospective analysis to describe associations between tumor necrosis factor alpha inhibitors and COPD-related hospitalizations.

BACKGROUND: Limited information exists on the impact of tumor necrosis factor inhibition on COPD exacerbations. This retrospective study characterized this impact among COPD patients with underlying autoimmune conditions, exposed to tumor necrosis factor inhibitors (TNFi) and/or non-biologic disease-modifying antirheumatic drugs (DMARDs). PATIENTS AND METHODS: Adult COPD patients with ≥1 diagnosis for rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) before or within 6 months following the index COPD diagnosis were identified from the Truven Health MarketScan® databases. Patients were required to have a second claim for RA, PsO, PsA, AS, or DMARD use (biologic or non-biologic) prior to or up to 6 months following the index date. Incidence of COPD-related hospitalizations and emergency room (ER) visits was evaluated in relation to treatment with TNFi and/or DMARDs and other potential risk factors. RESULTS: The study cohort included 40,687 patients (untreated, 37.7%; non-biologic DMARD, 35.4%; TNFi + non-biologic DMARD, 18%; TNFi, 8.8%). The proportion of patients with a COPD-related hospitalization and the incidence of COPD-related hospitalization (per 100 person-years) were lowest in the TNFi cohort (8.6%; 3.54, 95% confidence interval [CI]: 3.16-3.95) and the TNFi + non-biologic DMARD cohort (8.4%; 2.85, 95% CI: 2.63-3.08). In multivariate models, treatment with TNFi + non-biologic DMARD reduced the risk of COPD-related hospitalization or ER visits by 32% relative to non-biologic DMARDs (hazard ratio: 0.68; 95% CI: 0.61-0.75). CONCLUSION: In real-world settings, TNFi monotherapy confers similar risk for COPD-related hospitalization or ER visits as a non-biologic DMARD. Decreased risk was found among those treated with both TNFi and a non-biologic DMARD.

Mapping of Multiple Sclerosis Walking Scale (MSWS-12) to five-dimension EuroQol (EQ-5D) health outcomes: an independent validation in a randomized control cohort.

BACKGROUND: Mapping of patient-reported outcomes to the five-dimension EuroQol (EQ-5D) health index is increasingly being used for understanding the relationship of outcomes to health states and for predicting utilities that have application in economic evaluations. The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome that assesses the impact of walking impairment in people with MS. An equation for mapping the MSWS-12 to the EQ-5D was previously developed and validated using a North American Research Committee on MS (NARCOMS) registry cohort. MATERIALS AND METHODS: This analysis retested the validity of the equation mapping the MSWS-12 to the three-level EQ-5D (EQ-5D-3L) by using an independent cohort of patients with MS enrolled in a randomized controlled trial. Mapping was evaluated at two separate time points (baseline and week 4) during the clinical trial. The mapping equation's performance was subsequently assessed with mean absolute error (MAE) and root-mean-square error (RMSE) by comparing equation-based estimates to values elicited in the trial using the actual EQ-5D-3L questionnaire. RESULTS: The mapping equation predicted EQ-5D-3L values in this external cohort with reasonable precision at both time points (MAE 0.116 and RMSE 0.155 at baseline; MAE 0.105 and RMSE 0.138 at week 4), and was similar to that reported in the original NARCOMS cohort (MAE 0.109 and RMSE 0.145). Also as observed in the original NARCOMS cohort, the mapping equation performed best in patients with EQ-5D-3L values between 0.50 and 0.75, and poorly in patients with values <0.50. CONCLUSION: The mapping equation performed similarly in this external cohort as in the original derivation cohort, including a poorer performance in MS patients with more severe health-state severity.

Common flaws exist in published cost-effectiveness models of pharmacologic stroke prevention in atrial fibrillation.

OBJECTIVES: Decision makers use models to assist in evaluating the cost-effectiveness of pharmacologic stroke prevention in atrial fibrillation (SPAF). STUDY DESIGN AND SETTING: We performed a search of databases through October 3, 2012 to identify pharmacologic SPAF cost-effectiveness models. RESULTS: Of 30 identified models, 28 included warfarin, but only 60% assessed the impact of warfarin control on conclusions. Aspirin, dual antiplatelet, and newer anticoagulants were included in 41%, 10%, and 63% of models, respectively. Models used similar structures but included varying health states and made varying assumptions. They rarely reported performing a literature search to identify anticoagulant-specific inputs and used similar and older sources. Sixteen models used a lone randomized trial to reflect the efficacy and safety of main comparisons. One-third of models claimed a societal perspective; however, none included indirect costs. Patients typically initiated anticoagulation in the sixth or seventh decade of life and are followed for their lifetimes. Almost 70% of incremental cost-effectiveness ratios were below reported willingness-to-pay thresholds. All used deterministic sensitivity analyses and 77% conducted Monte Carlo simulation. Less than half of the models were rated "high quality," yet were frequently published in high-impact journals. CONCLUSION: Pharmacologic SPAF cost-effectiveness models have been extensively reported, but many may have flaws giving reason for decision makers to use caution. We provide 10 recommendations to avoid common flaws in SPAF cost-effectiveness models.

Impact of angina frequency on health utility values of patients with chronic stable angina.

BACKGROUND: Chronic angina is a profoundly symptomatic disease. We evaluated the relationship between angina frequency and health utility. METHODS: We used data from stable angina patients reporting ≥3 attacks/week enrolled in the Efficacy of Ranolazine in Chronic Angina (ERICA) trial. Angina frequency was classified using the Seattle Angina Questionnaire angina frequency (SAQAF) domain into no (100); monthly (61-99); weekly (31-60); and daily (0-30) angina. EuroQol (EQ)-5D health utility scores were derived from SAQ data using two mapping equations. Median EQ-5D utility scores for each SAQAF classification after the 6-week trial period were calculated (reported as: Equation 1/Equation 2). Changes in EQ-5D utility scores from baseline to end-of-trial for patients achieving and not achieving a ≥20-point improvement in SAQAF score and improving and not improving ≥1 SAQAF classification were compared. RESULTS: Median EQ-5D utility scores (n = 548) were 0.68/0.60. Compared to patients reporting no angina symptoms (n = 28; 0.89/0.87) patients reporting monthly (n = 188; 0.80/0.76), weekly (n = 283; 0.72/0.65) and daily (n = 49; 0.65/0.54) symptoms had poorer health utility (p < 0.001 for both equations). Patients improving ≥1SAQAF classification (n = 254/541, 47%) experienced a median 0.05/0.07 greater improvement in EQ-5D health utility compared to those not improving ≥1 classification (p < 0.001 for both equations). Patients improving ≥20-points on the SAQAF (n = 355/541, 66%) experienced a median 0.06/0.07 greater improvement in health utility compared to those not achieving a ≥20-point improvement (p < 0.001 for both). CONCLUSIONS: Chronic angina patient health utility decreases as angina frequency increases. Patients reporting clinically important improvement in angina frequency experience a tangible improvement in health utility. CLINICAL TRIAL REGISTRATION: NCT00091429.

Cost-effectiveness analysis of extended duration anticoagulation with rivaroxaban to prevent recurrent venous thromboembolism.

INTRODUCTION: Extended duration anticoagulation with rivaroxaban for an additional 6-12 months can reduce recurrent venous thromboembolic events (VTE) compared to placebo by ~82%, but at the detriment of increased bleeding. We sought to estimate the cost-effectiveness of extended duration prophylaxis of recurrent VTE with rivaroxaban. MATERIAL AND METHODS: A Markov model was developed to estimate the cost-effectiveness of extended duration rivaroxaban, 20mg daily, compared to placebo using a Medicare perspective, a one-monthcycle length and a 40-year time horizon. The model assumed a cohort of 58-year-old patients who had already completed an initial 6-12 months of anticoagulation with rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical equipoise with respect to the need for continued anticoagulation. Data sources included EINSTEIN-Extension and other published studies of VTE. Outcomes included direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Extended duration rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of bleeding and recurrent VTE, the hazard ratio of developing a recurrent event while on rivaroxaban and time horizon. Monte Carlo Simulation suggested rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Despite the cost of rivaroxaban and an increased risk of bleeding, extending VTE treatment for an additional 6-12 months with rivaroxaban was found cost-effective compared to the placebo over a 40-year time horizon.

Cost-effectiveness of ranolazine added to standard-of-care treatment in patients with chronic stable angina pectoris.

Ranolazine has been shown to decrease angina pectoris frequency and nitroglycerin consumption. We assessed the cost-effectiveness of ranolazine when added to standard-of-care (SoC) antianginals compared with SoC alone in patients with stable coronary disease experiencing ≥3 attacks/week. A Markov model utilizing a societal perspective, a 1-month cycle length, and a 1-year time horizon was developed to estimate costs (2013 US$) and quality-adjusted life years (QALYs) for patients receiving and not receiving ranolazine. Patients entered the model in 1 of the 4 angina frequency health states based upon Seattle Angina Questionnaire angina frequency (SAQAF) scores (100=no; 61 to 99=monthly; 31 to 60=weekly; and 0 to 30=daily angina) and were allowed to transition between states or to death based upon probabilities derived from the Efficacy of Ranolazine in Chronic Angina and other studies. Patients not responding to ranolazine in month 1 (not improving ≥1 SAQAF health state) were assumed to discontinue ranolazine and behave like SoC patients. Ranolazine patients lived a mean of 0.700 QALYs at a cost of $15,661. Those not receiving ranolazine lived 0.659 QALYs and at a cost of $14,321. The incremental cost-effectiveness ratio (ICER) for the addition of ranolazine was $32,682/QALY. The ICER was most sensitive to ranolazine cost but only exceeded $50,000/QALY when the cost of ranolazine increased >32% above base case. The ICER remained <$50,000/QALY when indirect costs were excluded, and mortality rates were assumed equivalent between SAQAF health states. Monte Carlo simulation found ranolazine cost-effective in 97% of 10,000 iterations at a $50,000/QALY willingness-to-pay threshold. In conclusion, ranolazine added to SoC is cost-effective in patients with weekly or daily angina.

Universal versus platelet reactivity assay-driven use of P2Y12 inhibitors in acute coronary syndrome patients: cost-effectiveness analyses for six European perspectives.

Platelet reactivity assays (PRAs) can predict patients' likely response to clopidogrel. As ticagrelor and prasugrel are typically considered first-line agents for acute coronary syndrome in Europe, we assessed the cost-effectiveness of universal compared to PRA-driven selection of these agents. A Markov model was used to calculate five-year costs (2013£/€), quality-adjusted life-years and incremental cost-effectiveness ratios (ICERs) for one-year of universal ticagrelor or prasugrel (given to all) compared to each agents' corresponding PRA-driven strategy (ticagrelor/prasugrel in those with high platelet reactivity [HPR, >208 on the VerifyNow P2Y12 assay], others given generic clopidogrel). We assumed patients had their index event at 65-70 years of age and had a 42.7% incidence of HPR 24-48 hours post-revascularisation. The analysis was conducted from the perspective of six countries (France, Germany, Italy, Spain, the Netherlands and United Kingdom) and used a one-year cycle length. Event data for P2Y12 inhibitors were taken from multinational randomised trials and adjusted using country-specific epidemiologic data. Neither universal ticagrelor nor prasugrel were found to be cost-effective (all ICERs >40,250€ or £36,600/QALY) compared to their corresponding PRA-driven strategies in any of the countries evaluated. Results were sensitive to differences in P2Y12 Inhibitors costs and drug-specific relative risks of major adverse cardiac events. Monte Carlo simulation suggested universal ticagrelor or prasugrel were cost-effective in only 25-44% and 11-17% of 10,000 iterations compared to their respective PRA-driven strategies, when applying a willingness-to-pay threshold = €30,000 or £20,000/QALY. In conclusion, the universal use of newer P2Y12 inhibitors is not likely cost-effective compared to PRA-driven strategies.

Timing of recurrent venous thromboembolism early after the index event: a meta-analysis of randomized controlled trials.

INTRODUCTION: Studies suggest a decreasing risk of recurrent venous thromboembolism (rVTE) in relation to time since the index event. We sought to conduct a meta-analysis examining the time course of rVTE over the first 3-months of anticoagulation. MATERIALS AND METHODS: A literature search of MEDLINE, EMBASE and CENTRAL (through 4/2013) was conducted to identify randomized trials of acute pharmacologic treatment and prevention of rVTE, enrolling ≥200 subjects/treatment arm, requiring anticoagulation for ≥3-months and reporting time-to-objectively-confirmed rVTE. Trials assessing extended-duration treatment, randomizing only cancer patients or not in English were excluded. Treatment arms were divided into monthly and weekly time periods for comparison (months 1-3 and weeks 1-12 after the index event). Treatment arm rVTE rates (per person-year) were pooled using a random-effects approach. RESULTS: Fifteen trials (31 treatment arms; n=27,237) were included. Higher rVTE rates were observed during the first month after the index event (0.19, 95% CI=0.16-0.23) compared to the second (0.05, 95% CI 0.04-0.06; p<0.001 vs. first month) and third months (0.02, 95% CI=0.02-0.03; p<0.001 vs. first month). While the highest rate of rVTE was in week 1 (0.29, 95% CI=0.21-0.37; p<0.01 vs. week 2), rates remained high through the fourth week (between 0.15 and 0.10 events/person-year) before decreasing and stabilizing at week 5 (≤0.05 events/person-year; p<0.01 vs. week 4). CONCLUSIONS: Our findings demonstrate a significant interaction between rVTE rates and time after the index event. High rVTE rates during the 3-4 weeks following the index event emphasize the importance of frequent surveillance during this time and the early optimization of pharmacologic therapy.

Mapping the 12-item multiple sclerosis walking scale to the EuroQol 5-dimension index measure in North American multiple sclerosis patients.

OBJECTIVE: To map the 12-item Multiple Sclerosis Walking Scale (MSWS-12) onto the EuroQol 5-dimension (EQ-5D) health-utility index in multiple sclerosis (MS) patients participating in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry. DESIGN: Cross-sectional MSWS-12 to EQ-5D cross-walking analysis. SETTING: NARCOMS registry spring 2010 biannual update and supplemental survey. PARTICIPANTS: North American patients completing both the MSWS-12 and the EQ-5D randomly split into derivation and validation cohorts. OUTCOME MEASURES: Ordinary least squares regression was performed within the derivation cohort, with participants' EQ-5D as the dependent variable. Results of the MSWS-12 were input as independent variable(s) into six regression models. Model goodness-of-fit was subsequently assessed in the validation cohort using the mean absolute error (MAE), root mean square error (RMSE) and the adjusted R(2). The best performing model was refined in the entire cohort and utilised for additional analyses. RESULTS: A total of 3505 NARCOMS participants were included. Their mean±SD EQ-5D and MSWS-12 scores were 0.74±0.18 and 50.8±33.5, respectively, and these assessments were found to be moderately correlated (r=-0.553, p<0.001). The model using all individual MSWS-12 item scores as independent variables was found to have the best fit (MAE=0.109±0.096, RMSE=0.145, adjusted R(2)=0.329). The percentage of EQ-5D estimates within 0.05 and 0.10 of the actual value were 30% and 61%, respectively. This mapping equation was more precise in patients with moderate mobility impairment (MAE=0.087±0.061 at patient-determined disease step (PDDS) of 3-6) and less precise in patients with no (MAE=0.141±0.128 at PDDS of 0-2) or severe mobility impairment (MAE=0.121±0.049 at PDDS ≥7). CONCLUSIONS: The EQ-5D scores can be predicted using the MSWS-12 item scores with reasonable precision in North American patients with MS. Prediction estimates were more precise in patients with moderate mobility impairment.

Estimation of the effect of dalfampridine-ER on health utility by mapping the MSWS-12 to the EQ-5D in multiple sclerosis patients.

BACKGROUND: Trials have not assessed the effect of dalfampridine-extended release (dalfampridine-ER) on health utility. We sought to evaluate the effect of dalfampridine-ER tablets (prolonged-release fampridine in Europe) on health utility in patients with multiple sclerosis (MS) by mapping subjects' individual item scores from the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) onto the Euroqol 5-Dimension (EQ-5D) health utility index. METHODS: Data from study MS-F203, a randomized trial of dalfampridine-ER tablets, 10 mg twice daily, in patients with MS, were used to calculate the health utility scores with two MSWS-12 to EQ-5D mapping equations (one derived in a North American [NA] registry, the other a United Kingdom [UK] registry). MS-F203 participants were categorized as dalfampridine-ER 20%-responders (achieving ≥20% improvement on the Timed 25-Foot Walk), dalfampridine-ER 20%-nonresponders (<20% improvement), or placebo patients. Mean change in health utility scores from baseline to each double-blind treatment evaluation (visits 3-6 occurring at post-randomization weeks 2, 6, 10, and 14) and each off-drug follow-up evaluation (visits 7-8 occurring at weeks 16 and 18) were calculated and reported as effect sizes (ESs). RESULTS: Using the NA-derived equation, dalfampridine-ER 20%-responders demonstrated improvement in health utility vs. placebo; starting at week 6 (mean difference in ES = 0.44, p = 0.002) and maintained at weeks 10 (ES = 0.41, p = 0.01) and 14 (ES = 0.71, p < 0.001). These improvements were no longer evident after dalfampridine-ER was discontinued (p > 0.05 at weeks 16 and 18). Dalfampridine-ER 20%-nonresponders did not show improvement vs. placebo at any visit (p > 0.05 for all). When using the UK-derived equation, improvement was seen in dalfampridine-ER 20%-responders vs. placebo at weeks 2, 6, 10, and 14 (ESs = 0.49, 0.55, 0.59, and 0.99; p < 0.03 for all), but not when dalfampridine-ER was discontinued (weeks 16 and 18; p > 0.05 for both). Dalfampridine-ER 20%-nonresponders showed no improvement at any visit (p > 0.05 for all). CONCLUSION: Regardless of the equation used, dalfampridine-ER response was associated with an improvement in health utility.

Cost-effectiveness of universal and platelet reactivity assay-driven antiplatelet therapy in acute coronary syndrome.

Assays monitoring P2Y12 platelet reactivity can accurately predict which patients will have a poor response to clopidogrel. We sought to determine the cost-effectiveness of using platelet reactivity assays (PRAs) to select a dual-antiplatelet regimen for patients with acute coronary syndrome. A hybrid decision tree Markov model was developed to determine the cost-effectiveness of universal clopidogrel, ticagrelor, or prasugrel (given to all patients) or PRA-driven ticagrelor or prasugrel (given to patients with high platelet reactivity, defined as >230 on the VerifyNow P2Y12 assay; the others received generic clopidogrel). We assumed a cohort of 65-year-old patients with acute coronary syndrome and an incidence of high platelet reactivity of 32% and 13% at ~24 to 48 hours after revascularization and 1 month, respectively. The 5-year costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were calculated for PRA-driven ticagrelor and prasugrel compared with universal clopidogrel, ticagrelor, or prasugrel. PRA-driven ticagrelor and prasugrel were cost-effective compared with universal clopidogrel (incremental cost-effectiveness ratio $40,100 and $49,143/quality-adjusted life-year, respectively); however, universal ticagrelor and prasugrel were not (incremental cost-effectiveness ratio $61,651 and $96,261/quality-adjusted life-year, respectively). Monte Carlo simulation suggested PRA-driven ticagrelor, PRA-driven prasugrel, universal ticagrelor, and universal prasugrel would have an incremental cost-effectiveness ratio <$50,000/quality-adjusted life-year in 52%, 40%, 23%, and 2% of the iterations compared with universal clopidogrel, respectively. Universal ticagrelor and prasugrel were not cost-effective compared with their respective PRA-driven regimens (incremental cost-effectiveness ratio $68,182; $116,875/quality-adjusted life-year, respectively). Monte Carlo simulation suggested universal ticagrelor and prasugrel would have an incremental cost-effectiveness ratio <$50,000/quality-adjusted life-year in 26% and 4% of iterations compared with their respective PRA-driven regimens. The results were most sensitive to differences in agent costs and drug-specific relative risks of death. In conclusion, even with generic clopidogrel, PRA-driven selection of antiplatelet therapy appeared to be a cost-effective strategy with the potential to decrease the overall acute coronary syndrome-associated healthcare costs.

Novel anticoagulants for stroke prevention in atrial fibrillation: a systematic review of cost-effectiveness models.

OBJECTIVE: To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF). PATIENTS AND METHODS: We searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF. RESULTS: Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results. CONCLUSIONS: Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.

Effect of pharmacist intervention on glycemic control in diabetes.

AIM: To conduct a meta-analysis evaluating the effect of pharmacist intervention on glycemic control. METHODS: A systematic search of Medline and CENTRAL was conducted from the earliest possible date through June 2010. Trials were included if they were randomized controlled trials in a diabetic population, evaluated any form of pharmacist intervention and reported data on hemoglobin A1C (A1C). A random-effects model was used to calculate weighted mean differences (WMDs) and 95% confidence intervals. RESULTS: Fourteen trials (n = 2073) evaluating the effect of pharmacist intervention on glycemic control were identified. Pharmacist intervention significantly lowered A1C (n = 14 trials, WMD -0.76%, 95%CI -1.06 to -0.47) and fasting blood glucose (FBG) (n = 4 trials, WMD -29.32 mg/dL, 95%CI -39.54 to -19.10). A moderate to high degree of statistical heterogeneity was observed in these analyses (I(2) ≥ 44.1% for both). CONCLUSIONS: Our findings demonstrate statistically and clinically significant associations between pharmacist intervention and improvement in glycemic control.